EFNA4_HUMAN
ID EFNA4_HUMAN Reviewed; 201 AA.
AC P52798; C9JHJ8; G3XAK2; O95457; Q5SR71; Q6FI57;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ephrin-A4;
DE AltName: Full=EPH-related receptor tyrosine kinase ligand 4;
DE Short=LERK-4;
DE Flags: Precursor;
GN Name=EFNA4; Synonyms=EPLG4, LERK4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7838529;
RA Kozlosky C.J., Maraskovsky E., McGrew J.T., Vanden Bos T., Teepe M.,
RA Lyman S.D., Srinivasan S., Fletcher F.A., Gayle R.B. III, Cerretti D.P.,
RA Beckmann M.P.;
RT "Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs
RT encoding a family of proteins.";
RL Oncogene 10:299-306(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=B-cell;
RX PubMed=10607706;
RA Aasheim H.-C., Munthe E., Funderud S., Smeland E.B., Beiske K.,
RA Logtenberg T.;
RT "A splice variant of human ephrin-A4 encodes a soluble molecule that is
RT secreted by activated human B lymphocytes.";
RL Blood 95:221-230(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 26-40.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
CC -!- FUNCTION: Cell surface GPI-bound ligand for Eph receptors, a family of
CC receptor tyrosine kinases which are crucial for migration, repulsion
CC and adhesion during neuronal, vascular and epithelial development.
CC Binds promiscuously Eph receptors residing on adjacent cells, leading
CC to contact-dependent bidirectional signaling into neighboring cells.
CC May play a role in the interaction between activated B-lymphocytes and
CC dendritic cells in tonsils.
CC -!- INTERACTION:
CC P52798; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-5241592, EBI-348587;
CC P52798; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-5241592, EBI-11988865;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Lipid-anchor, GPI-
CC anchor.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=GPI-anchored;
CC IsoId=P52798-1; Sequence=Displayed;
CC Name=2; Synonyms=Secreted;
CC IsoId=P52798-2; Sequence=VSP_001448;
CC Name=3;
CC IsoId=P52798-3; Sequence=VSP_046707;
CC -!- TISSUE SPECIFICITY: Expressed in the adult spleen, lymph node,
CC prostate, ovary, small intestine, and colon, and in fetal heart, lung,
CC liver and kidney. Also detected in hematopoietic cell lines.
CC -!- SIMILARITY: Belongs to the ephrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00884}.
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DR EMBL; U14188; AAC50079.1; -; mRNA.
DR EMBL; AJ006352; CAA06992.1; -; mRNA.
DR EMBL; AJ006353; CAA06993.1; -; mRNA.
DR EMBL; CR533569; CAG38600.1; -; mRNA.
DR EMBL; AL691442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53138.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53139.1; -; Genomic_DNA.
DR EMBL; BC107483; AAI07484.1; -; mRNA.
DR CCDS; CCDS1089.1; -. [P52798-1]
DR CCDS; CCDS41407.1; -. [P52798-2]
DR CCDS; CCDS44237.1; -. [P52798-3]
DR PIR; I38850; I38850.
DR RefSeq; NP_005218.1; NM_005227.2. [P52798-1]
DR RefSeq; NP_872631.1; NM_182689.1. [P52798-3]
DR RefSeq; NP_872632.2; NM_182690.2. [P52798-2]
DR AlphaFoldDB; P52798; -.
DR SMR; P52798; -.
DR BioGRID; 108265; 162.
DR DIP; DIP-48295N; -.
DR IntAct; P52798; 4.
DR STRING; 9606.ENSP00000414378; -.
DR GlyConnect; 1211; 1 N-Linked glycan (1 site).
DR GlyGen; P52798; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; P52798; -.
DR PhosphoSitePlus; P52798; -.
DR BioMuta; EFNA4; -.
DR DMDM; 1706672; -.
DR EPD; P52798; -.
DR jPOST; P52798; -.
DR MassIVE; P52798; -.
DR PaxDb; P52798; -.
DR PeptideAtlas; P52798; -.
DR PRIDE; P52798; -.
DR ProteomicsDB; 33769; -.
DR ProteomicsDB; 56536; -. [P52798-1]
DR ProteomicsDB; 56537; -. [P52798-2]
DR Antibodypedia; 34875; 293 antibodies from 29 providers.
DR DNASU; 1945; -.
DR Ensembl; ENST00000359751.8; ENSP00000352789.4; ENSG00000243364.8. [P52798-2]
DR Ensembl; ENST00000368409.8; ENSP00000357394.3; ENSG00000243364.8. [P52798-1]
DR Ensembl; ENST00000427683.2; ENSP00000414378.2; ENSG00000243364.8. [P52798-3]
DR GeneID; 1945; -.
DR KEGG; hsa:1945; -.
DR MANE-Select; ENST00000368409.8; ENSP00000357394.3; NM_005227.3; NP_005218.1.
DR UCSC; uc001fhc.4; human. [P52798-1]
DR CTD; 1945; -.
DR DisGeNET; 1945; -.
DR GeneCards; EFNA4; -.
DR HGNC; HGNC:3224; EFNA4.
DR HPA; ENSG00000243364; Tissue enhanced (skin).
DR MIM; 601380; gene.
DR neXtProt; NX_P52798; -.
DR OpenTargets; ENSG00000243364; -.
DR PharmGKB; PA27659; -.
DR VEuPathDB; HostDB:ENSG00000243364; -.
DR eggNOG; KOG3858; Eukaryota.
DR GeneTree; ENSGT00940000162071; -.
DR HOGENOM; CLU_081598_3_0_1; -.
DR InParanoid; P52798; -.
DR OMA; VCCKESR; -.
DR OrthoDB; 1094764at2759; -.
DR PhylomeDB; P52798; -.
DR PathwayCommons; P52798; -.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling.
DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR SignaLink; P52798; -.
DR SIGNOR; P52798; -.
DR BioGRID-ORCS; 1945; 14 hits in 1081 CRISPR screens.
DR GeneWiki; EFNA4; -.
DR GenomeRNAi; 1945; -.
DR Pharos; P52798; Tbio.
DR PRO; PR:P52798; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P52798; protein.
DR Bgee; ENSG00000243364; Expressed in skin of leg and 119 other tissues.
DR Genevisible; P52798; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; TAS:ProtInc.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IBA:GO_Central.
DR CDD; cd10425; Ephrin-A_Ectodomain; 1.
DR Gene3D; 2.60.40.420; -; 1.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR031328; Ephrin.
DR InterPro; IPR034252; Ephrin-A_Ecto.
DR InterPro; IPR019765; Ephrin_CS.
DR InterPro; IPR001799; Ephrin_RBD.
DR PANTHER; PTHR11304; PTHR11304; 1.
DR Pfam; PF00812; Ephrin; 1.
DR PRINTS; PR01347; EPHRIN.
DR SUPFAM; SSF49503; SSF49503; 1.
DR PROSITE; PS01299; EPHRIN_RBD_1; 1.
DR PROSITE; PS51551; EPHRIN_RBD_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 26..170
FT /note="Ephrin-A4"
FT /id="PRO_0000008373"
FT PROPEP 171..201
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000008374"
FT DOMAIN 26..155
FT /note="Ephrin RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT LIPID 170
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 58..99
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT DISULFID 86..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00884"
FT VAR_SEQ 157..201
FT /note="KSESAHPVGSPGESGTSGWRGGDTPSPLCLLLLLLLLILRLLRIL -> NLP
FT SHPKEPESSQDPLEEEGSLLPALGVPIQTDKMEH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10607706"
FT /id="VSP_001448"
FT VAR_SEQ 157..201
FT /note="KSESAHPVGSPGESGTSGWRGGDTPSPLCLLLLLLLLILRLLRIL -> RAR
FT VLPRSPGGGGIPAACTGGANSDRQDGALMGEIRGSEVTLAGACPLITG (in
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046707"
SQ SEQUENCE 201 AA; 22386 MW; ABE8D5443A9AF28D CRC64;
MRLLPLLRTV LWAAFLGSPL RGGSSLRHVV YWNSSNPRLL RGDAVVELGL NDYLDIVCPH
YEGPGPPEGP ETFALYMVDW PGYESCQAEG PRAYKRWVCS LPFGHVQFSE KIQRFTPFSL
GFEFLPGETY YYISVPTPES SGQCLRLQVS VCCKERKSES AHPVGSPGES GTSGWRGGDT
PSPLCLLLLL LLLILRLLRI L
